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Background: Complex regional pain syndrome (CRPS) is a disabling painful disorder caused by many different and poorly understood mechanisms. It often affects the distal limbs and usually happens as consequence of a trauma. Its severity can remarkably affect patients' quality of life. When this painful complication happens in a cancer patient, the impact may be exponential. To date, there is limited knowledge of the surrounding circumstances of CRPS cases in this population. Methods: We present two clinical cases of patients diagnosed with cancer-related pain presenting with symptoms and signs compatible with CRPS. In one case, CRPS was attributed to direct tumor nerve compression, and it responded successfully to an interventional pain procedure. The second case was associated with a Zoster infection in an immunocompromised cancer patient. Patient responded to multidisciplinary pain management strategies. Additionally, we conducted a literature review to investigate the coexistence of cancer pain and CRPS and suggest some pathophysiology mechanisms of action. Results and Discussion: Literature reviewed and potential pathophysiology mechanisms are simultaneously explored in terms of classification, etiopathology, evidence, challenges, and future scientific directions. Conclusion: Comorbid CRPS can impact negatively in cases of cancer pain by affecting their diagnosis and treatment. Further studies are necessary to elucidate how these two conditions present together and how they can be better addressed. [ABSTRACT FROM AUTHOR]